Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Institute of Clinical Physiology, IFC CNR, Messina Unit, Messina, Italy.
Allergy. 2015 Apr;70(4):436-42. doi: 10.1111/all.12571. Epub 2015 Jan 29.
Mastocytosis is characterized by clonal proliferation of mast cells limited to the skin (cutaneous mastocytosis: CM and mastocytosis in the skin: MIS) and/or involving internal organs (systemic mastocytosis: SM). Oxidative stress occurring in various inflammatory and neoplastic disorders causes molecular damage with the production of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs). We evaluated these markers of oxidative stress in patients with CM/MIS and SM and correlated their levels with the presence of symptoms related to mast cell activation.
Serum levels of AOPPs and AGEs in 34 patients with mastocytosis (23 CM/MIS and 11 SM) and 27 healthy controls were measured by spectrofluorimetric and spectrophotometric methods. Serum tryptase levels were measured by immunofluorescence.
Serum AOPPs, but not AGEs, were significantly higher in patients with mastocytosis as compared to healthy controls. While serum tryptase levels were higher in patients with SM as compared to those with CM/MIS, there was no difference in AOPP and AGE concentrations between these two groups of patients. Patients with recurrent mediator-related symptoms had lower AOPPs and AGEs as compared to patients without symptoms. AOPPs and AGEs were inversely correlated with the severity of symptoms, and in patients with symptoms, AOPPs correlated with tryptase levels.
Our data show that mastocytosis is associated with a state of increased oxidative stress that, in patients with mediator-related symptoms, correlates with mast cell burden as assessed by tryptase. Patients with symptoms presumably have an adaptive response resulting in lower blood levels of AOPPs and AGEs.
肥大细胞增多症的特征是局限于皮肤的肥大细胞克隆性增殖(皮肤肥大细胞增多症:CM 和皮肤外肥大细胞增多症:MIS)和/或累及内脏器官(系统性肥大细胞增多症:SM)。在各种炎症和肿瘤性疾病中发生的氧化应激导致分子损伤,产生高级氧化蛋白产物(AOPPs)和晚期糖基化终产物(AGEs)。我们评估了 CM/MIS 和 SM 患者这些氧化应激标志物的水平,并将其与与肥大细胞活化相关的症状的存在相关联。
通过分光荧光法和分光光度法测量 34 例肥大细胞增多症患者(23 例 CM/MIS 和 11 例 SM)和 27 例健康对照者的血清 AOPPs 和 AGEs 水平。通过免疫荧光法测量血清胰蛋白酶水平。
与健康对照组相比,肥大细胞增多症患者的血清 AOPPs,但不是 AGEs,明显升高。虽然 SM 患者的血清胰蛋白酶水平高于 CM/MIS 患者,但两组患者的 AOPP 和 AGE 浓度无差异。与无症状患者相比,反复发作的介质相关症状患者的 AOPPs 和 AGEs 较低。AOPPs 和 AGEs 与症状的严重程度呈负相关,在有症状的患者中,AOPPs 与胰蛋白酶水平相关。
我们的数据表明,肥大细胞增多症与氧化应激增加的状态相关,在有介质相关症状的患者中,与通过胰蛋白酶评估的肥大细胞负荷相关。有症状的患者可能具有适应性反应,导致 AOPPs 和 AGEs 的血液水平较低。